Publications by authors named "Kevin M Tuffy"
Article Synopsis
- Nirsevimab is a long-lasting monoclonal antibody designed to prevent RSV-related respiratory issues in vulnerable infants and children, and its effectiveness was tested against the standard treatment, palivizumab, in a clinical trial called MEDLEY.
- The trial included two RSV seasons where participants received either nirsevimab or palivizumab, with ongoing assessments of RSV infections and antibody responses through nasal swabs.
- The results showed that while certain substitutions in RSV isolates developed resistance to palivizumab, no changes were found that affected nirsevimab's ability to neutralize RSV, indicating its potential superiority in preventing RSV infections.
Objectives: The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) necessitates rapid methods for assessing monoclonal antibody (mAb) potency against emerging variants. Authentic virus neutralisation assays are considered the gold standard for measuring virus-neutralising antibody (nAb) titres in serum. However, authentic virus-based assays pose inherent practical challenges for measuring nAb titres against emerging SARS-CoV-2 variants (e.
View Article and Find Full Text PDFArticle Synopsis
- Nirsevimab is a modified monoclonal antibody designed to prevent respiratory syncytial virus (RSV) infections in infants and works through direct virus neutralization and potential Fc-mediated immune responses.
- The study investigated Nirsevimab and its variants to see how they bind to immune receptors and whether they enhance protective immune functions like phagocytosis and cytotoxicity.
- Results show Nirsevimab has strong immune activity similar to palivizumab, effectively reducing RSV in preclinical models, but it did not increase antibody-dependent cellular cytotoxicity (ADCC) compared to a placebo.
Article Synopsis
- * Analysis showed that RSV A and B infections occurred at similar rates, with some noteworthy substitutions in their fusion proteins affecting susceptibility to nirsevimab.
- * Despite some binding site changes, over 99% of RSV isolates from the trials remained sensitive to nirsevimab, indicating its continued effectiveness.
Background: We report spike protein-based lineage and AZD7442 (tixagevimab/cilgavimab) neutralizing activity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants identified from breakthrough infections in the PROVENT preexposure prophylaxis trial.
Methods: Variants identified from PROVENT participants with reverse-transcription polymerase chain reaction-positive symptomatic illness were phenotypically assessed to determine neutralization susceptibility of variant-specific pseudotyped virus-like particles.
Results: At completion of 6 months' follow-up, no AZD7442-resistant variants were observed in breakthrough coronavirus disease 2019 (COVID-19) cases.
Nirsevimab binding-site conservation in respiratory syncytial virus fusion glycoprotein worldwide between 1956 and 2021: an analysis of observational study sequencing data.
Lancet Infect Dis
July 2023
Article Synopsis
- Nirsevimab, a long-lasting monoclonal antibody developed to protect infants from RSV, shows great potential due to the high conservation of its binding site, although the emergence of escape variants needs further investigation from 2015 to 2021.
- The study analyzed RSV A and B prevalence across multiple global surveillance studies, revealing that most amino acids in the nirsevimab binding site remained stable, with only a notable polymorphism (Ile206Met:Gln209Arg) appearing in RSV B after 2016.
- The researchers found that nirsevimab effectively neutralizes various RSV strains, including some with binding-site changes, although certain RSV B variants showed reduced sensitivity to nirsevim
Article Synopsis
- Therapeutic monoclonal antibodies (MAbs) like AZD7442 offer protective and treatment options for people at high risk for COVID-19, specifically targeting the SARS-CoV-2 virus.* -
- The study examined how effectively AZD7442 neutralizes different Omicron subvariants, finding that BA.2 and its derivatives are more susceptible than BA.1 and BA.1.1, with BA.4/BA.5 falling in between.* -
- Continued monitoring of SARS-CoV-2 variants is essential to ensure that MAbs remain effective, especially as the virus evolves and new variants emerge.*
AZD7442, a combination of two long-acting monoclonal antibodies (tixagevimab [AZD8895] and cilgavimab [AZD1061]), has been authorized for the prevention and treatment of coronavirus disease 2019 (COVID-19). The rapid emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants requires methods capable of quickly characterizing resistance to AZD7442. To support AZD7442 resistance monitoring, a biolayer interferometry (BLI) assay was developed to screen the binding of tixagevimab and cilgavimab to SARS-CoV-2 spike proteins to reduce the number of viral variants for neutralization susceptibility verification.
View Article and Find Full Text PDFObjectives: Robust, quantitative serology assays are required to accurately measure antibody levels following vaccination and natural infection. We present validation of a quantitative, multiplex, SARS-CoV-2, electrochemiluminescent (ECL) serology assay; show correlation with two established SARS-CoV-2 immunoassays; and present calibration results for two SARS-CoV-2 reference standards.
Methods: Precision, dilutional linearity, ruggedness, analytical sensitivity and specificity were evaluated.
Article Synopsis
- Despite the success of COVID-19 vaccines, there is still a need for additional prevention and treatment methods for at-risk individuals.
- AZD7442 is a combination of two monoclonal antibodies that target different parts of the SARS-CoV-2 spike protein, effectively neutralizing the virus and preventing its entry into human cells.
- Clinical studies suggest that AZD7442 can provide long-lasting protection, potentially up to 12 months, especially benefiting those at higher risk for severe COVID-19 outcomes.
Article Synopsis
- Understanding how the immune system recognizes the SARS-CoV-2 spike protein can help improve treatment options for COVID-19.
- Researchers studied two human monoclonal antibodies, AZD8895 and AZD1061, to see how they bind to the virus's receptor-binding domain (RBD) and why they are effective in neutralizing the virus.
- They found that unique structural features of these antibodies contribute to their strong neutralizing abilities against SARS-CoV-2 and its variants, suggesting the potential effectiveness of the antibody cocktail AZD7442 in combating new strains.
The ability of the retroviral Gag protein of Rous sarcoma virus (RSV) to transiently traffic through the nucleus is well-established and has been implicated in genomic RNA (gRNA) packaging Although other retroviral Gag proteins (human immunodeficiency virus type 1, HIV-1; feline immunodeficiency virus, FIV; Mason-Pfizer monkey virus, MPMV; mouse mammary tumor virus, MMTV; murine leukemia virus, MLV; and prototype foamy virus, PFV) have also been observed in the nucleus, little is known about what, if any, role nuclear trafficking plays in those viruses. In the case of HIV-1, the Gag protein interacts in nucleoli with the regulatory protein Rev, which facilitates nuclear export of gRNA. Based on the knowledge that RSV Gag forms viral ribonucleoprotein (RNPs) complexes with unspliced viral RNA (USvRNA) in the nucleus, we hypothesized that the interaction of HIV-1 Gag with Rev could be mediated through vRNA to form HIV-1 RNPs.
View Article and Find Full Text PDFPackaging of genomic RNA (gRNA) by retroviruses is essential for infectivity, yet the subcellular site of the initial interaction between the Gag polyprotein and gRNA remains poorly defined. Because retroviral particles are released from the plasma membrane, it was previously thought that Gag proteins initially bound to gRNA in the cytoplasm or at the plasma membrane. However, the Gag protein of the avian retrovirus Rous sarcoma virus (RSV) undergoes active nuclear trafficking, which is required for efficient gRNA encapsidation (L.
View Article and Find Full Text PDFUnlabelled: Influenza A and B viruses cocirculate in humans and together cause disease and seasonal epidemics. These two types of influenza viruses are evolutionarily divergent, and exchange of genetic segments inside coinfected cells occurs frequently within types but never between influenza A and B viruses. Possible mechanisms inhibiting the intertypic reassortment of genetic segments could be due to incompatible protein functions of segment homologs, a lack of processing of heterotypic segments by influenza virus RNA-dependent RNA polymerase, an inhibitory effect of viral proteins on heterotypic virus function, or an inability to specifically incorporate heterotypic segments into budding virions.
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